探讨Alpha-2肾上腺素受体作用剂经抑制HDACs减少败血症急性肾损伤作用.pdfVIP

2011年中华医学会全困麻醉学术年会论文汇编 探讨Alpha．2肾上腺素受体作用剂 经抑制HDACs减少败血症急性肾损伤的作用 邢中熹1一，陈贞吟1，康富期1，王志中1，陈大梁2，叶静华3 1奇美医学中心麻醉部2台北医学大学医学院麻醉学科3长荣大学医学研究所 背景 细胞素在败血症急性肾损伤具有重要角色，组织蛋白去乙酰基酵素 Histone dexmedetomidine DEX 对HDAC作用及保护败血症急性。肾损伤的机制。 材料与方法 在小鼠CLP手术后立即暨12 BMP．7，HDAC2，and 因表现情形。 结果 24 and DEX可增加败血症小鼠存活并减少肾损伤。CLP MCP．1 及MCP．1但减少BMP．7基因表达； DEX的作用。在BMP．7基因剔除NRK52E细胞，DEX可增加LPS刺激后BMP一7mRNA表达，DEX也 histoneH3。 降低HDAC2及HDAC5并增加acetylated 结论 histone H3而达到细胞素基因调控作用。本研究提出DEX在败血症肾损 HDAC2、HDAC5增加acetylated 伤可能的保护机制。 of on acute via HDACs alpha-2adrenergicreceptoragonistreducingkidneyinjuryinhibiting Investigation sin septicmice in a criticalrole acute injury AKI during BackgroundCytokineexpressionplays kidney chromatinstructure．Activationofalpha-2 deacetylase HDAC regulatesgeneexpressionbymodifying reduceAKIin theeffectsof alpha·2 receptormay sepsis．Thisstudyinvestigated adrenergicreceptor adrenergic 635 2011年中华医学会全国麻醉学术年会论文汇编 HDACs and AKL agonistdexmedetomidine DEX onprotectionagainstsepsis-induced MaterialsandmethodsMiceweretreatedwinlDEXorsaline and12hoursafterCLP immediately surgery． as HDAC5 weredetermined． TNF—a，MCP·l，BMP一7，HDAC2，and Survival，ki血eyinjury，雏wdl expressions In BMP．7mRNAweredeterminedinLPStreatedns．or vitro，HDAC2，HDAC5，TNF—a，MCP．1，and ratrenaltubular cell orwithoutan siBMP一7-NRK52E line，with cells，a epithelial alpha-2 survivalandattenuated√Uq 24hof ResultsDEXincreased ofCLPmice．After mRNA andMCP．1 wereincreasedbutBMP．7mRNAweredecreasedinthe treatment kidney．however,DEX attenuatedthose increased andMCP—lbutdecreasedBMP-7 changes．Invitro，LPS HDAC2，HDAC5，硼、JF．a mRNAinaratrenaltubular eellline．NRK52Ecells．DEXincreasedBMP．7butdecreasedTNF．aand epithelial MCP-lmRNA inLPS-stimulatedN鼬为2E wereaRenuateda11A2AR expression cells，which bv antagonist， BMP．7．knockdownN麟2E yohimbine．In cells．DEXincreasedBMP．7mRNAandreducedcelldeathafter LPS—stimulation．DEXalsodecreasedHDAC2andHDAC5mRNAsandincreased histoneH3in acetylated LPS．stimulatedNRK52Ecells．whicheffe